CASK is a protein which has been identified to be of importance in cell-cell signaling related to the neurexin neuronal cell surface protein family. The cytoplasmid domain of neurexin proteins interact with a small, 84 residue PDZ domain of CASK. The current project is aimed at understanding, at the molecular level, this binding process. Central to this effort is solving the three dimensional structure of the PDZ domain, which we have done by X-ray crystallography. With the protein structure in hand we now plan to determine the binding conformation of peptides homologous to the presumed binding region of the neurexins by multidimensional heteronuclear NMR. We have made significant progress on this effort. In collaboration with Dr. Chris Turner and Dr. Susan S. Pochapsky we have recorded several 2DH-"N-HSQC spectra on the uncomplexed and peptide bound PDZ domain and have verified that the binding event will significantly perturb amide chemical shifts of a number of key residues. Additionally, we have recorded 3D 1H,"N-filtered NOESY-HSQC and TOCSY-HSQC spectra of the two forms. These spectra will aid significantly in the spectral assignment and the determination of the binding mode of the peptide.